Many techniques for determining the presence of and measuring the concentration of various analytes in human blood are known in the art. These include invasive procedures involving the extraction of samples with needles or syringes and examination in an extra-corporeal analyser or the insertion in a blood vessel of a catheterized sensor and the measurement of blood parameters in vivo.
The development of non-invasive blood monitors or sensors is comparatively new, particularly for the determination of glucose concentration.
Although blood glucose levels in people without diabetes vary very little, usually staying within the range of about 4 to 7 mmol./L.; in people who have diabetes blood glucose levels vary considerably, even after treatment with insulin. The variation of glucose levels in diabetes tends to follow a fairly predictable pattern.
Medical evidence shows that the control of blood sugar, primarily glucose, levels in diabetics reduces the risk of the complications often resulting from diabetes. Accordingly, many samples may be taken for analysis during the course of a single day. The analysis is used to determine whether insulin or extra food or a glucose tablet is required to adjust an abnormal high or low glucose concentration.
The self-monitoring of blood glucose by the patient is considered by many clinicians to be the most important advance in the treatment of diabetes since the discovery of insulin. Because many patients consider the finger-lancing necessary for self-monitoring to be painful, inconvenient and embarrassing, and moreover, self-monitoring tends to be expensive, a less invasive method is clearly desirable.
U.S. Pat. Nos. 5,028,787 and 5,086,229 disclose an instrument and method for measuring blood glucose using near infrared energy introduced into a vein or artery of a subject, detecting the emerging signal in a detector which provides an electrical signal and processing the signal to provide a read-out indicative of the glucose concentration.
U.S. Pat. No. 5,070,874 discloses a method and apparatus for non-invasive determination of the concentration of glucose in a patient which uses near infrared radiation over a narrow range of wavelengths about 1660 nanometers (nm), derives a first and second expression as functions of the wavelength and determines the glucose concentration by calculations from said expressions.
Biological tissue is relatively transparent to near infrared (NIR) radiation having a wavelength within the range of about 700 to 1100 nm. U.S. Pat. No. 5,070,874 also refers to "near infrared" radiation, but the method disclosed therein relates to radiation of a somewhat longer wavelength in the region of 1660 nm. Although there is no universal definition of the range of wavelengths for NIR and wavelengths from 600 to 2500 nm have been quoted; as used herein NIR radiation is defined as radiation having a wavelength within the aforesaid range of about 700 to 1100 nm. Thus, the radiation used in the device and method of the present invention is clearly distinct from that used in the method of U.S. Pat. No. 5,070,874, and the significance of this distinction will be apparent from the description hereinafter.
The technique underlying the present invention is predicated upon the transparency of biological tissue to NIR radiation and is designated herein as pulse NIR spectroscopy. In this technique the NIR radiation transmitted through or reflected from biological tissue, for example, tissue located in a finger or ear-lobe, is filtered and detected. The radiation detected consists of a pulsatile component and a constant component. The constant component results from the absorption of radiation by skin, bone, tissue, venous and mixed venous blood, which are all constant light absorbers. The varying, pulsatile component results uniquely from the pulsating arterial blood in the path of the radiation. The magnitude of the pulsatile component at a glucose-sensitive wavelength is related to the glucose concentration in arterial blood. By using a technique involving the pulsatile component only, the influence of the constant or static absorbers is eliminated.
Although the procedure disclosed in U.S. Pat. Nos. 5,028,787 and 5,086,229 uses near infrared energy, the disclosure does not differentiate between the various tissue components, for example, venous and arterial blood, and there is no disclosure or suggestion of detecting and measuring the pulsatile component only. It has now been found that by taking measurements on the pulsatile component only the complex and expensive instrumentation required for prior art procedures may be eliminated and a low-cost device providing accurate non-invasive measurement of a desired analyte, particularly glucose, in arterial blood may be made. The measurements are made at a glucose-sensitive wavelength and at a reference wavelength. A relationship is then established between the ratio (R) of these two measurements and the blood glucose concentration determined from drawn blood samples. This relationship is incorporated in the monitoring device and forms the basis for subsequent non-invasive glucose concentration measurement.